1. Field of the Invention
The present invention relates to: a) synthetic glyceollin I and glyceollin II, both as a mixture and as pure glyceollin I and pure glyceollin II; b) methods of synthesizing synthetic glyceollin I and glyceollin II; and c) methods of using synthetic glyceollin I and II.
2. Description of Related Art
The glyceollins (GLYs) are natural product compounds that display properties indicative for use as cancer prevention and treatment agents. See, e.g., N. T. Keen, J. L. Ingham, T. Hymowitz, J. J. Sims, S. Midland, Biochem. System. Ecol. 1989, 17, 395-398; V. Persky, L. Van Horn, J. Nutr. 1995, 125, 709S-712S; C. Herman et al., J. Nutr. 1995, 125, 757S-770S; B. M. Collins-Burow, M. E. Burow, B. N. Doung, J. A. McLachlan, Nutr. Cancer 2000, 38, 229-244; M. E. Burow et al., J. Clin. Endrocrinol. Metab. 2001, 86, 1750-1758; and V. A. Salvo et al., Clin. Cancer Res. 2006, 12, 7159-7164, each of which is hereby incorporated by reference in its entirety. To date, supplies of the GLYs must be obtained by their induced biosynthesis in soybean plant parts followed by tedious extraction and purification procedures which provide extremely low yields. See, e.g., T. Komives, J. Chrom. 1983, 261, 423-424; J. Huang, K. R. Barker, Plant Physiol. 1991, 96, 1302-1307; C. Kraus, G. Spiteller, A. Mithoefer, J. Ebel, Phytochem. 1995, 40, 739-743; R. Hammerschmidt, Ann. Rev. Phytopath. 1999, 96, 285-306; H. M. G. Al-Hazimi, H. Z. Alkhathlan, J. King Saud Univ. Sci. 2000, 12, 93-122; S. M. Boue, C. H. Carter, K. C. Ehrlich, T. E. Cleveland, J. Agric. Food Chem. 2000, 48, 2167-2172; J. Faghihi, X. Jiang, R. Vierling, S. Goldman, S. Sharfstein, J. Sarver, P. Erhardt, J. Chrom. A 2001, 915, 61-74; and T. E. Cleveland, S. M. Boue, M. E. Burow, J. A. McLachlan, U.S. Pat. Appl. Pub. No. 20060246162, each of which is hereby incorporated by reference in its entirety. Thus, there is an immediate need for improved methods to produce various GLY compounds for further development, as well as a longer-term need for producing large supplies of selected GLY members for eventual use within the marketplace. See, e.g., R. S. Khupse, P. W. Erhardt, 30th National Medicinal Chemistry Symposium, Seattle, June 2006, Poster #87; and R. S. Khupse, P. W. Erhardt, 234th National ACS Meeting, Boston, August 2007, Poster #MEDI-182, each of which is hereby incorporated by reference in its entirety. The present invention provides very practical methods for synthesizing GLYs I and II in higher yields than can be obtained by their extraction from induced soybean. In addition, these methods can be used to prepare a variety of GLY-related compounds, including glycinol and certain synthetic intermediates that have novel compositions of matter. The purified, individual GLY members, synthetic intermediates and selected analogs display useful pharmacological properties similar to the naturally-derived materials.